Mitochondrial disease and stroke.

BACKGROUND AND PURPOSE: It is well known that some mitochondrial disorders are responsible for ischemic cerebral infarction in young patients. Our purpose was to determine, in this prospective ongoing study, whether ischemic stroke is the only manifestation of a mitochondrial disorder in young patients. METHODS: Patients aged

Mitochondrial DNA point mutation in the COI gene in a patient with McArdle's disease.

We studied a 57-year-old female patient with clinical and biochemical evidences of McArdle's disease. Her muscle biopsy also revealed signs of mitochondrial proliferation, scattered RRF, and a deficit in complex I of the respiratory chain. Molecular genetic analysis showed that the patient was heterozygous for the most common mutation at codon 49 in the myophosphorylase gene. Mitochondrial DNA analysis of muscle tissue revealed an additional G-to-A transition at nucleotide position 7444 in the cytochrome c oxidase subunit I (COI) gene.

[Recurrent familial brachial plexopathy as the only clinical expression of neuropathy with susceptibility to pressure]. / Plexopatía braquial recurrente familiar como única expresión clínica de una neuropatía con susceptibilidad a la presión.

We report a family with hereditary neuropathy with liability to pressure palsies (HNPP) and chromosome 17p11.2 deletion. This family exhibits a peculiar phenotype consisting in recurrent brachial plexopathy episodes. This phenotype has to be distinguished from hereditary neuralgic amyotrophy on clinical grounds. Although the incidence of brachial plexopathy on HNPP is relatively high it is unusual as the sole symptom of the disease. It is noteworthy that in the six published families with this peculiar phenotype most of the acute episodes became evident after sleep. A greater liability of the plexus and a greater vulnerability to mechanical factors during sleep hours are the suggested mechanisms to explain this rare clinical onset. Recurrent painless brachial plexopathy when associated to generalized conduction abnormalities should suggest a HNPP.

Plexopatía braquial recurrente familiar como única expresión clínica de una neuropatía con una susceptibilidad a la presión / Recurrent familial brachial plexopathy as the only clinical expression of neuropathy with susceptibility to pressure

Presentamos una familia con neuropatía hereditaria con susceptibilidad a la presión (NHSP), portadora de la deleción 17p11.2, con un fenotipo clínico peculiar consistente en parálisis recurrentes del plexo braquial. Este fenotipo de NHSP debe distinguirse clínicamente de la amiotrofia neurálgica hereditaria. Aunque la incidencia de plexopatía braquial en la NSHP es relativamente alta, es bastante inusual que constituya la única manifestación clínica de la enfermedad. En las seis familias hasta ahora descritas con este fenotipo es de destacar que el factor desencadenante más frecuente de los episodios lo constituye el sueño. Una mayor susceptibilidad del plexo braquial y una mayor vulnerabilidad del mismo a factores mecánicos durante las horas de sueño son propuestas para explicar esta presentación clínica inusual. La plexopatía braquial recurrente no dolorosa asociada a anomalías difusas de conducción debe hacer sospechar una NSHP (AU)

Lipomatosis, proximal myopathy, and the mitochondrial 8344 mutation. A lipid storage myopathy?

Multiple symmetric lipomatosis (MSL) has been related in some cases to the 8344 point mutation of the tRNA-lysine gene of the mitochondrial DNA, mainly in the context of families with classic myoclonic epilepsy with ragged-red fibers (MERRF) and exceptionally in patients with proximal myopathy as the only manifestation of mitochondrial disease. We report on two families harboring the 8344 mutation. The patients presented with MSL and myopathy, expressed as limb girdle weakness in index cases and as exercise intolerance in the others. All muscle biopsies performed showed lipid storage apart from RRF and respiratory chain complexes deficiency. A possible explanation for both adipose proliferation and lipid storage myopathy in these cases is a disturbance in intermediary lipid metabolism secondary to mitochondrial respiratory chain deficiency that could be related via carnitine deficiency.

[Mitochondrial encephalomyopathy of late presentation with progressive ophthalmoplegia, tremor and diffuse leukoencephalopathy]. / Encefalomiopatía mitocondrial de presentación tardía, con oftalmoplejía externa progresiva, temblor y leucoencefalopatía difusa.

A 60-year-old woman had developed ptosis, progressive external ophthalmoplegia and action tremor over the last ten years. Physical examination also revealed short stature and retinal pigmentation. Anaerobic forearm exercise test showed increase of basal lactate and rise of lactate/piruvate index. Biceps biopsy displayed numerous ragged red fibers. Respiratory chain studies were consistent with complex I deficiency. Point mutations or deletions in mitochondrial DNA were not found. MR identified a diffuse leukoencephalopathy over both cerebral hemispheres, mesencephalon, pons and cerebellum. The late and sporadic onset of a progressive external ophthalmoplegia outlining a Kearns-Sayre syndrome is striking. A leukoencephalopathy associated with mitochondrial encephalomyopathy is an infrequent finding. The action tremor of this patient could be symptomatic of her mitochondrial disfunction.

[The bent spine syndrome: a focal axial myopathy of late onset]. / Síndrome de "bent spine": una miopatía focal axial de inicio tardío.

The bent spine is a rare syndrome appearing at an advanced age which shows a posture of anterior flexion of the trunk, which is reducible and is often hereditary. It is caused by a paresia of the extensor musculature of the trunk by a focal axial myopathy of late onset. We herein describe the case of a 72-year-old woman with a progressive bent spine initiated at the age of 55. Family questioning showed vertical transmission of the process. On exploration paresis of the paravertebral musculature and to a lesser extent of both girdles was observed. Serum CK levels were normal. Vertebral CT showed atrophy with fatty substitution of the paravertebral musculature. EMG of the scapular and paravertebral muscles demonstrated a myopathic pattern. Deltoid muscle biopsy found atrophy of type II fibers and isolated broken red fibers. This case corroborates the myopathic nature of this syndrome. A review of the nosology of the syndrome is also presented.

Myophosphorylase deficiency associated with a defect in complex I of the mitochondrial respiratory chain.

We studied a 21-year-old patient with clinical, biochemical and histochemical evidence of myophosphorylase deficiency and unusual repetitive episodes of pigmenturia. His muscle biopsy also revealed morphological signs of mitochondrial proliferation and a defect of complex I of the respiratory chain. His mother had exercise intolerance without myoglobinuria and no histochemical evidence of myophosphorylase deficiency. In muscle, the mother showed some ragged-red fibers, normal respiratory chain levels and a significant residual phosphorylase activity. Molecular genetic analysis revealed that the proband was homozygous for the mutation commonly found in McArdle's disease. The mother, father, and the five siblings were all heterozygous for the same mutation. Mitochondrial DNA analysis of the proband's muscle failed to demonstrate known mutations associated with his clinical pattern. Moreover, we sequenced his tRNA(Leu(UUR)) gene, a hot spot for mutations, showing no abnormality.

[Usefulness of cerebral biopsy in focal cerebral lesions in patients with human immunodeficiency virus infection]. / Utilidad de la biopsia cerebral en las lesiones cerebrales focales en pacientes con infección por el virus de la inmunodeficiencia humana.

Brain mass lesions (BML) occurred in 10% of patients infected by the human immunodeficiency virus (HIV), as expression of severe and sometimes treatable diseases. However, the management of them is not well established. We analyzed, retrospectively, 26 brain biopsies (22 estereotaxic) in patients with HIV infection and BML to know their usefulness and safety. The inclusion criteria were: Failure of the anti-Toxoplasma empirical treatment, atypical scan appearance for toxoplasmosis, or severe neurological picture. Brain biopsy yielded a diagnosis in 19 patients (73.1%): Progressive multifocal leukoencephalopathy (n = 8; 30.8%), primary central nervous system lymphoma (n = 6; 23.1%), mycobacteriosis (n = 2; 7.7%), toxoplasmosis (n = 2; 7.7%), criptococcosis (n = 1), cryptosporidiosis (n = 1) and HIV-encephalitis (n = 1). In one case there was a multiple diagnosis: mycobacteriosis, toxoplasmosis, and lymphoma. Brain biopsy results decided a change in therapy in 65.4%, the resolution or improvement of the neurological process in 30.8%, and the determination of the prognosis in 30.8%. In 8 cases (30.7%) there were biopsy complications, with secondary mortality in one. Brain biopsy of BML in HIV-infected patients is a diagnostic method with a high overall diagnostic rentability and uncommon non reversible complications, offering the possibility to prescribe a specific and potentially curative treatment.

[Adult onset mitochondrial myopathy without ophthalmoplegia. Four cases attributable to complex III and IV deficits in the respiratory chain]. / Miopatía mitocondrial de inicio en la edad adulta sin oftalmoplejía. Presentación de 4 casos por déficit de complejos III y IV de la cadena respiratoria.

Four adults with proximal myopathy of mitochondrial origin but no ocular involvement are presented. Biochemical analysis showed combined complex III and IV deficits in the respiratory chain in all cases, suggesting an apparent correlation between clinical phenotype and biochemical findings. Mitochondrial DNA analysis of muscle from 1 patient failed to detect either large-scale deletion or point mutations at position 3243 of tRNA(Leu(UUR)) or at 8344 of tRNA(Lys). The tissue specificity of the disease and the absence of family history suggest that a mutation in a nuclear DNA gene encoding a specific subunit of muscle could underlie this disease.

[Chronic demyelinating polyneuropathy associated with multiple sclerosis: a patient with two diseases]. / Polineuropatia crónica desmielinizante asociada a esclerosis múltiple. Un paciente y dos enfermedades.

We studied the clinical, paraclinical and laboratory findings of a patient suffering from multiple sclerosis (MS) with chronic demyelinating polyneuropathy. As well as being a new case of demyelination of the central and peripheral nervous system not normally associated with the presence of antiganglionic antibodies, our patient presented clinical signs distinct from each disease with the characteristic abnormalities of cerebrospinal fluid (CSF) (cytological albumin dissociation at the moment when an outbreak appeared at the peripheral level and an increase in intrathecal secretion when the outbreak was at the central nervous system level). Demyelinating diseases of the central and peripheral nervous systems are a field of great interest in trying to find the antigenic bull's eye for MS.

[Congenital myopathy with cores and nemaline rods in one family]. / Miopatía congénita con cores y bastones nemalínicos en la misma familia. Asociación a un síndrome del túnel carpiano.

We present a mother and 2 children with congenital myopathy whose clinical signs were facial paresis in all three, and mild involvement of the lower extremities in the mother and one son. All three presented skeletal abnormalities, hypertelorism, arched palate, retraction of the Achilles tendon or short neck. Symptoms were not progressive and muscle biopsies showed central cores and nemaline rods in the mother and only nemaline rods in the 2 sons. The mother also suffered carpal tunnel syndrome, as had other members of the family as the result of autosomal dominant inheritance.

[Recessive distal myopathies. Five cases]. / Miopatías distales recesivas. Aportación de cinco casos.

We present five patients with distal weakness in the lower extremities with onset in adolescence. Paresis tended to occur in the gastrocnemia in 3 patients and was accompanied by marked elevation of CPK (> 10 times higher than normal). Muscle biopsies showed signs of dystrophy. The clinical picture for these patients was consistent with the diagnosis of recessive distal myopathy (Miyoshi's form). The differential sign in the other 2 cases was greater involvement of the anteroexternal leg muscles and the presence of rimmed vacuoles similar to those characteristic of Nonaka's vacuolar distal myopathy.

[Pulmonary tumorlets in POEMS syndrome]. / Tumorlets pulmonares en el síndrome POEMS.

POEMS syndrome is a systemic disease characterized by severe chronic polyneuropathy, organomegaly (adenopathy, and liver enlargement) endocrinopathy, monoclonal peak, sclerotic bone lesions and skin changes. We report on a case of complete POEMS syndrome with peripheral arterial thrombosis and multiple lung tumorlets. No antibodies were found against human nervous tissues or Rhesus monkey on patient serum. This case is the first association described of POEMS syndrome and lung tumorlets.

[Complex I (NADH coenzyme-Q-reductase) deficiency, MELAS syndrome and hypertrophic cardiomyopathy]. / Déficit de complejo I (NADH coenzima-Q-reductasa), síndrome MELAS y miocardiopatía hipertrófica.

A 24-year-old male had a deficiency of the complex I (NADH coenzyme-Q-reductase) of the mitochondrial respiratory chain, which clinically presented as a mitochondrial encephalomyopathy, with lactic acidosis and stroke-like episodes (MELAS syndrome). The encephalopathic episodes were preceded by migraine and were characterized by focal deficit signs, motor partial seizures and hypodense areas in the CT scan. An echocardiographic diagnosis of hypertrophic cardiomyopathy without intracavitary thrombi was made. It is suggested that hypertrophic cardiomyopathy is caused by the mitochondrial abnormalities that have been reported in the myocardium, and that migraine and cerebral infarctions are associated with abnormalities in the mitochondria from the endothelium and smooth muscle fibres of the cerebral small arteries and arterioles.

Continuous muscle activity and distal spinal muscular atrophy.

A young man presented with myokymias, cramp-like difficulty in muscle relaxation and peroneal atrophy. EMG studies revealed continuous muscle activity (CMA) manifested as grouped potentials and high frequency discharges. Sensory nerve conduction studies and sural nerve biopsy gave normal results, and he was thought to suffer from distal spinal muscular atrophy with CMA. This association suggests that the lower motor neuron may have an important role in the generation of the continuous muscle activity.

[Multifocal demyelinating neuropathy with persistent conduction blocks and continuous muscular activity]. / Neuropatía desmielinizante multifocal con bloqueos de conducción persistentes y actividad muscular continua.

A patient developed an initially asymmetric sensory-motor neuropathy, with definite predominance in upper limbs. The examination also disclosed a markedly impaired muscle relaxation. The neurophysiological study showed conduction blocks with continuous muscle activity consisting of myokymias fasciculations and muscle cramps which disappeared after the anesthetic block of the distal nerve segments. In the sural nerve biopsy significant abnormalities were not found. After prednisone and carbamazepine therapy in usual doses the symptoms reverted and the conduction blocks persisted. Neuropathy with persistent conduction blocks is an uncommon disease which exceptionally results in a clinically apparent syndrome of continuous muscle activity. Its recognition is important, as symptoms can disappear after correct therapy.